A recent study by researchers at the University of Pittsburgh has overturned a decades-old assumption in neuroscience: that both spontaneous and evoked synaptic transmissions rely on the same neural machinery and sites. Published in Science Advances, the findings reveal that the brain actually employs separate transmission sites to manage different types of neuroplasticity, offering fresh insights into how the brain maintains a balance between stability and adaptability, two pillars essential to learning, memory, and mental health.

Typically, neurons transmit information by releasing neurotransmitters from a presynaptic terminal into the synaptic cleft, where they bind to postsynaptic receptors. It was long assumed that both random (spontaneous) and experience-driven (evoked) transmissions emerged from the same synaptic site.

However, using a mouse model, the team led by Dr. Oliver Schlüter found otherwise. Their experiments focused on the primary visual cortex, where early visual processing occurs. They observed that after the onset of visual input, evoked transmissions continued to develop and strengthen, whereas spontaneous transmissions leveled off. This indicates that each type of transmission follows a distinct developmental path and is governed by different regulatory mechanisms.

To test this, researchers applied a compound that activates silent postsynaptic receptors, leading to an increase in spontaneous activity without affecting evoked responses. This clearly demonstrates that the two types of signaling rely on functionally independent synaptic sites.

The study suggests this separation allows the brain to sustain homeostasis via spontaneous signaling, while simultaneously enabling Hebbian plasticity, the process of strengthening neural connections based on experience and activity.

“This dual signaling system may be the brain’s way of being both stable and adaptable,” said Yue Yang, the study’s first author. “Understanding this architecture helps explain how the brain manages complex learning while avoiding instability”.The implications are wide-ranging. Disruptions in synaptic signaling are associated with disorders such as autism, Alzheimer’s disease, and addiction. A clearer picture of how signaling works in the healthy brain could lead to better understanding and perhaps treatment of these conditions.